Fungus farmers show way to new drugs

In a mutually beneficial symbiosis, leaf-cutting ants cultivate fungus gardens, providing both a safe home for the fungi and
a food source for the ants. But this 50-million-year-old relationship also includes microbes that new research shows could
help speed the quest to develop better antibiotics and biofuels.

Ten years ago, Cameron Currie, a microbial ecologist then at the University of Toronto in Ontario, Canada, discovered that
leaf-cutting ants carry colonies of actinomycete bacteria on their bodies (C. R. Currie et al. Nature398,701–704; 1999). The bacteria churn out an antibiotic that protects the ants' fungal crops from associated parasitic fungi (such as
Escovopsis). On 29 March, Currie, Jon Clardy at the Harvard Medical School in Boston and their colleagues reported that they had isolated
and purified one of these antifungals, which they named dentigerumycin, and that it is a chemical that has never been previously
reported (D.-C. Oh et al. Nature Chem. Bio.doi: 10.1038/nchembio.159; 2009). The antifungal slowed the growth of a drug-resistant strain of the fungus Candida albicans, which causes yeast infections in people.

“These ants are walking pharmaceutical factories.

Because distinct ant species cultivate different fungal crops, which in turn fall prey to specialized parasites, researchers
hope that they will learn how to make better antibiotics by studying how the bacteria have adapted to fight the parasite in
an ancient evolutionary arms race. "These ants are walking pharmaceutical factories," says Currie, now at the University
of Wisconsin, Madison.

That's not the end to the possible applications. The ant colonies are also miniature biofuel reactors, Currie reported on
25 March at the Genomics of Energy & Environment meeting at the Joint Genome Institute in Walnut Creek, California. Each year,
ants from a single colony harvest up to 400 kilograms of leaves to feed their fungal partners. But no one has worked out how
the fungi digest the leaves, because samples of fungus grown in petri dishes can't break down cellulose, a tough molecule
found in plant cells. Researchers are keenly interested in better ways to break down cellulose, because it might allow them
to make more efficient biofuels than those made from sugary foods, such as maize (corn).

So Currie and his colleagues sequenced small segments of DNA from bacteria and other organisms living in fungus gardens in
three Panamanian leaf-cutting ant colonies. They then compared the DNA against databases to identify what species were living
in the fungus gardens, and what genes they contained.

This 'metagenomics' approach found that there are many species of bacteria in the fungus gardens that are capable of breaking
down cellulose. The team also detected the genetic signatures of fungal enzymes that can break down cellulose, which raises
the question of why the fungi can't break down cellulose in the laboratory.

Currie suggests that the newfound bacterial and fungal enzymes might be efficient at digesting cellulose because they have
evolved for centuries along with the ant-fungal symbiosis. This could mean that the fungus can only break down cellulose in
its natural context, or that the enzymes Currie detected are brought into the colony from outside. "The idea is that the ants'
long evolutionary history may help us in our own attempts to break down plant biomass," he says.

Other researchers call Currie's findings interesting, but say they wanted to see a more thorough analysis of the data. "It's
interesting that he found these fungal enzymes in the gardens that he didn't expect [based on] what the fungus was capable
of doing by itself," says John Taylor, a mycologist at the University of California, Berkeley.

Taylor says that Currie's continued scrutiny of the lives of ants provides insights into the web of interactions necessary
for the survival of any single species. "I think the coolest thing about this is that you start with one organism, and then
you find more and more organisms involved in the relationship," he says. It may take a village to raise a child; it seems
it also takes a village to break down cellulose.